New Potential Antisense Drug for DM1

Researchers from Isis Pharmaceuticals collaborated with university teams from across North America to test out what could be the next generation of antisense drugs targeting myotonic dystrophy type 1 (DM1). As our community knows, the potential therapy currently in a phase I/II clinical trial, IONIS-DMPKRx, is also an antisense drug.

As with the IONIS-DMPKRx antisense technology, this drug again targets the molecule believed to be responsible for causing toxicity in people with DM1: the mRNA (known as ‘toxic RNA’) containing a large repeat made from the DMPK gene. In this newer approach researchers modified the drug slightly to see if it could target the DMPK mRNA more strongly, and penetrate different tissues more efficiently.

Ionis Pharmaceuticals first tested more than 600 versions of this new modification in cells. The company then picked out a few of the most potent and well tolerated drugs and tested these on mice and rats. The tests identified the top candidate, which was then tested in monkeys.

Isis found that this newer drug was able to reduce DMPK mRNA by up to 70% in some muscles, and 50% in the heart. This new antisense drug was also long lasting, as it was still detected in muscle tissue 13 weeks after the final dose was administered. Overall, the drug was safe and effective at targeting the DMPK mRNA, and may be considered for future use in drug trials.